ABSTRACT
Benign prostatic hyperplasia therapy has evolved over the last two decades from a simple choice between watchful waiting and transurethral resection of the prostate to more complex treatment decisions between various medical therapies and an expanding range of minimally invasive treatment options. Most patients who suffer some degree of bother from their benign prostatic hyperplasia-associated symptoms will now opt for medical therapy in the first instance. Plant extracts from a variety of sources are popular, especially in continental Europe, but there is little hard evidence from randomized trials of their efficacy and safety. α-Blockers, such as doxazosin, tamsulosin and alfuzosin, can all be administered once per day and produce rapid and sustainable improvement of lower urinary tract symptoms and uroflow (Figure 82)55. It has been argued that tamsulosin, which has selectivity for the α1A and α1D adrenoceptor subtypes, and alfuzosin, which is also relatively ‘uroselective’ (i.e. has more impact on prostate obstruction than blood pressure) have some advantages over doxazosin and terazosin, which have a balanced effect on all three receptor subtypes. However, doxazosin reduces the blood pressure in hypertensive men but has little or no impact on the blood pressure of normotensive individuals56. Doxazosin also reduces platelet adhesiveness and reduces LDL cholesterol, and thus may offer some cardiovascular protection in addition to improvement of lower urinary tract symptoms and uroflow57. Both doxazosin and terazosin, but not tamsulosin or alfuzosin, have been shown to cause apoptosis within the prostate, and it has been argued that this may rebalance the proliferative processes that underlie the condition (Figure 83). However, the clinical utility of this effect is still unproven. The 5α-reductase type 2 inhibitor, finasteride, at a dose of 5 mg/day, effectively reduces prostate volume by around 20% and improves symptoms and uroflow almost to the same extent as the α-blockers, but only after a 3-6-month treatment period58. Available evidence suggests that finasteride works most effectively in men with a clinically enlarged prostate and a PSA value over 1.5 ng/ml; this effect is well maintained over 6 years of follow up. The Proscar Long-term Efficacy and Safety Study (PLESS) has demonstrated that finasteride can reduce benign prostatic hyperplasia-associated complications such as acute urinary retention and the need for prostate surgery by more than 50%59. This beneficial impact of medical therapy on benign prostatic hyperplasia progression has been confirmed
by the Medical Therapy of Prostate Symptoms (MTOPS) study60, which has been recently reported. In this 4.5-year trial, the combination of finasteride and doxazosin was significantly more effective than either agent alone or identical placebo in terms of preventing benign prostatic hyperplasia progression, defined as a 4-point or greater rise in symptom score, or development of acute retention or the need for benign prostatic hyperplasia-related surgery (Figure 84). The overall risk of progression, mostly due to symptomatic progression, was reduced by 39% for doxazosin, 34% for finasteride and 67% for combination therapy, respectively. The risk of acute retention was reduced by 31% for doxazosin, 67% for finasteride and 79% for combination therapy, while the risk of prostate-related surgery was reduced by 64% and 67%, respectively for finasteride and combination therapy with no significant change in risk noted for the doxazosin group compared with placebo. The novel agent dutasteride can be distinguished from finasteride by its ability to inhibit both type 1 and type 2 isoforms of 5α-reductase. Recent data confirm that this compound also significantly improves lower urinary tract symptoms and uroflow in men with an enlarged prostate61 with a side-effect profile rather similar to finasteride. Roehrborn and colleagues have confirmed that serum PSA can act as a surrogate for prostate volume62, and that 5α-reductase inhibitors are used most effectively in men with PSA values >1.5 ng/ml63,64.
